Several viral and bacterial live recombinant vaccine vehicles are being developed to produce a new generation of vaccines against a broad spectrum of infectious diseases (Bloom, B. R., Nature 342:115-120 (1989)). The human tuberculosis vaccine Mycobacterium bovis bacillus Calmette-Guerin (M. bovis-BCG or BCG) (Calmette et al., Bull. Acad. Natl. Med. (Paris) 91:787-796 (1924)) has features that make it a particularly attractive live recombinant vaccine vehicle. BCG and other mycobacteria are highly effective adjuvants, and the immune response to mycobacteria has been studied extensively. With nearly 2 billion immunizations, BCG has a long record of safe use in man (Luelmo, F., Am. Rev. Respir. Dis. 125:70-72 (1982) and Lotte et al., Adv. Tuberc. Res. 21:107-193 (1984)). It is one of the few vaccines that can be given at birth, it engenders long-lived immune responses with only a single dose, and there is a worldwide distribution network with experience in BCG vaccination.
To date, vaccines have been developed which, although effective in many instances in inducing immunity against a given pathogen, must be administered more than once and may be unable to provide protection, on a long-term basis, against a pathogen. In addition, in many cases (e.g., leprosy, malaria, etc.), an effective vaccine has yet to be developed.